DESCRIPTION: (Applicant's Description) Basal Cell Carcinomas (BCCs) are the commonest human cancer and are of increasing incidence, due in part to increased recreational sunlight exposure. During the past two years, the fundamental molecular defect apparently underlying the aberrant behavior of these tumor cells has been uncovered; all BCCs have abnormal regulation of the hedgehog signaling pathway. Patients with the basal cell nevus syndrome (BCNS) are susceptible to developing multiple basal cell carcinomas because they inherit one defective allele of the PTC gene, which encodes a protein that hampers hedgehog signaling. Mice hemizygous for a functioning ptc gene, like BCNS patients with the same genotype, are highly susceptible to the development of BCCs, and these are induced by the relevant environmental insult-ultraviolet light. This project will utilize the growing knowledge of HCC signaling aberrations, the murine BCC model, and the chemopreventive effects of tea extracts to develop agents efficacious in preventing BCC carcinogenesis in mice and man and will investigate the mechanisms underlying such efficacy.